Jill Termaat, MD; Elizabeth Wheatley, MD; Michael V. Bloom, PhD; Treatment in the face of Jerome W. Freeman, MD; Mark K. Huntington, MD, PhD uncertainty following traumatic Center for Family Medicine, Sioux Falls, SD (Drs. Termaat, Wheatley, anhydrous ammonia exposure Bloom, and Huntington); Department of Neuroscience (Dr. Freeman) and The patient lost consciousness and his vision. He then Department of Family Medicine (Drs. Bloom and experienced incomplete sight recovery, anxiety, and Huntington), Sanford School of Medicine, Sioux Falls recurring . How would you proceed

[email protected] with his care?

The authors reported no potential conflict of interest relevant to this article.

is a previously healthy 33-year-old A month later, an ophthalmologist reex- D white man, married and father amined JD and, again, found no cause for the J of 2 children, who, while working as an ocular abnormality and suggested artificial agronomist, was inadvertently exposed to tears for dry eyes. Two months later, he saw anhydrous ammonia. His only recollection an optometrist, who documented constrict- of the event was a "puff of smoke” and the ed visual fields and referred JD to a second smell of ammonia. He lost consciousness ophthalmologist. This consultant suggested almost immediately and awoke several days possible brain injury and doubted it was psy- later in the intensive care unit. He was blind. chosomatic in nature. He referred the patient Over the days that followed, he regained to a neurologist. The neurologist found no or- central vision; however, the loss of peripheral ganic explanation for his vision loss. He sus- vision in all fields persisted. He said that pected a somatoform disorder and told JD his upon first waking in the morning, he could vision should recover. JD and his wife initially "only see shadows.” For the rest of the day, declined the neurologist’s idea of a neuro- he had “tunnel vision.” Ophthalmology and ophthalmology consultation, but eventually evaluations uncovered no obvious agreed. The neuro-ophthalmologist also sus- reasons for the persistent vision loss. pected a functional disturbance as the cause The patient also complained of mild for ; and he required the headache and discomfort behind his eyes for patient to stop driving a motor vehicle until which he was taking aspirin. The discomfort his vision improved. behind his left eye was worse than on the The patient was subsequently referred right. He remained on disability following for psychological evaluation. When initially his work injury, and began to feel increas- seen by a psychologist and a family medicine ingly distressed and hopeless. His wife noted resident, JD was working as a farmhand to he was uncharacteristically irritable with her make ends meet. and the children, and that he had vivid night- mares and said he could smell ammonia. He What symptoms are typical of also had trouble keeping up his yard because Q anhydrous ammonia exposure? of the agitation and anxiety he experienced in approaching his workshed and equipment on the property.

710 The Journal of Family Practice | DECEMBER 2013 | Vol 62, No 12 Effects of ammonia exposure dia of the eye (cornea, lens, etc), the retina, or Ammonia is a water-soluble, colorless gas— the neural visual pathways. It may also have an alkaloid with a unique odor. In the past, a psychogenic component.5 Media-related most exposures were related to its use as a fer- causes of acute vision loss include keratitis tilizer, as was the case with JD. In recent years, or uveitis, edema of the cornea, blood in the it has also been used to illegally manufacture anterior chamber (hyphema), disturbance of methamphetamine, which has led to ammo- the lens, or hemorrhage into the vitreous.5,6 nia accidents and increased exposures.1-3 Retinal causes include occlusion of the cen- Systems commonly injured are the respi- tral retinal artery or vein, detachment of the ratory tract, ocular system, skin, and gastro- retina, or acute maculopathy.5-8 Neurologic intestinal tract (only if ingested).2 causes include injury to the optic nerve it- Ammonia destroys the mucosal barrier of self (normally monocular) or defects in the the respiratory tract, causing loss of cilia, edema, chiasmal or retrochiasmal regions (causing and smooth muscle contraction.3,4 Long-term partial loss in both eyes).5,9 If all of the above effects include chronic cough or hoarseness, possibilities have been ruled out, consider obstructive or restrictive airway disease, reac- psychogenic contribution to visual loss.5 Of- tive airway disease, or bronchiectasis.1,3 ten this diagnosis is called “functional vision The extent of ocular injury is related to loss,” which can include feigning visual loss the degree of ammonia exposure. In mild for secondary gain or subjective blindness as cases, there is eye irritation, increased tear is seen with a somatoform disorder (eg, con- When you production, a sensation of stinging or burn- version disorder). suspect a ing, and perhaps conjunctivitis or spasmodic JD had bilateral peripheral vision loss of somatoform winking. The patient may also experience both the medial and lateral visual fields with disorder, photophobia.1,3,4 In more severe cases, there macular sparing bilaterally. But he had an oth- including may be corneal ulcerations, iritis, anterior erwise normal physical examination. At this conversion, or posterior synechia, opacification of the point, the neurologist suspected conversion start therapy cornea, cataracts, glaucoma, atrophy of the disorder, while one ophthalmologist thought a and treat the retina, or severe pain.1,3 Blindness may occur, neuropathic disorder was responsible. symptoms as temporarily or permanently.4 This complete “real.” or partial vision loss is secondary to physical What is your working diagnosis damage that can be seen during an ophthal- Q for this patient’s symptoms? mologic examination.1,4 Skin injuries can range from a mild ery- thematous rash to a full thickness burn with bullae and even denudation.1 Long-term ef- fects include scarring or dermatitis.3 What are some of the Our patient had respiratory and skin Q psychological sequelae of symptoms that fit with classic ammonia ex- traumatic events such as the one posure (respiratory distress requiring in- this patient experienced? tubation, rash). His initial blindness was consistent with ammonia exposure; however, his subsequent peripheral loss was inconsis- tent with known reaction to ammonia. The neurologist had, early on, recognized What are some of the causes of that JD was significantly distressed by the ac- Q acute visual loss? cident and encouraged a psychological con- sultation. With the absence of identifiable ophthalmologic pathology, the patient reluc- tantly accepted this referral. The psychologist, aided by family medi- Causes of acute visual loss cine residents, entertained the diagnoses of Vision loss can be caused by injury to the me- Post-Traumatic Disorder (PTSD) and

jfponline.com Vol 62, No 12 | DECEMBER 2013 | The Journal of Family Practice 711 somatoform disorders, particularly conversion. essary to begin treatment. When you suspect PTSD is unique among psychiatric diagnoses a somatoform disorder including conver- in that a patient must meet all 6 DSM V criteria:10 sion, start therapy and treat the symptoms as • exposure to a traumatic event involving ac- “real.”12 Tell the patient that no specific treat- tual or threatened death or serious injury ment will completely resolve the symptoms, • recollections, dreams, or hallucinations but that it can help.13 Whether the primary in which the trauma is re-experienced cause is neurologic or conversion based, • avoidance of stimuli associated with the there is often some spontaneous recovery of trauma vision that occurs between 2 weeks and 3 or • persistent symptoms of increased arous- more months.14 Peripheral field defects have al (eg, irritability, agitation) a guarded prognosis, although an extensive • symptoms and behavior that last for lon- rehabilitation program may improve the vi- ger than one month sion fields somewhat.15-18 • distress that is clinically significant. Conversion disorders effectively respond to cognitive behavioral therapy (CBT) includ- He met the criteria for a PTSD diagnosis ing gradual exposure to anxiety triggers.19 Re- and likely would benefit from treatment for it. habilitation for neurologic damage based on However, sensory loss related to PTSD alone remodeling of pathways responds to a similar would be unusual, perhaps as unusual as pe- gradual exercise or exposure to the lost func- CBT, including ripheral vision loss secondary to ammonia ex- tion. Since these interventions are similar gradual posure. Other factors needed to be explored. processes, a definitive diagnosis was unnec- exposure to Conversion disorders consist of disorders essary in JD’s case. A proprietary visual reha- anxiety triggers, of movement, such as seizures or , or bilitation therapy program is available17 that is effective both disorders of sensations, such as numbness or exposes the patient to visual field activity that for treating blindness. These may be episodic or sustained requires a cognitive reaction.15 This treatment conversion and have acute or chronic onset.11 facilitates recovery even into the sixth month disorders and Psychological factors are judged to be as- of therapy.16 However, the cost of the software for rehabilitating sociated with the symptom or deficit because is approximately $6000 and is not yet covered damaged conflicts or other stressors precede the initia- by insurance.15 neurologic tion or exacerbation of the symptom or deficit. JD could not afford the commercially pathways. This was possible in JD, but a degree of uncer- available programmed therapy. Therefore, we tainty lingered because he did not exhibit be- introduced an alternative treatment plan to havior typically seen with , challenge the transitional zone. With this plan, and performance anxiety could conceivably JD would play video games for 30 minutes at account for the outcome on his vision tests. least twice a week, and preferably daily. He sat In general, he could meet the criteria for close enough to the television so that the tran- conversion disorder, but questions remained. sitional zone was approximately 1 to 2 inches The biggest question is whether the accident from the peripheral portion of the television resulting in PTSD is the cause of the psycho- screen. The game was an action-packed video logical stress, or is the peripheral vision loss in which the peripheral portion of the screen the source of the , which was important (such as in first-person shooter would mean it is not a conversion disorder? games). He was to continue staring at the cen- ter of the screen during play in order to truly how would you treat this patient? exercise the peripheral vision. Every day, he Q reassessed where the transitional zone was located and adjusted his seating accordingly. JD practiced this at least once a day and found that he had to sit closer and closer to the tele- vision screen to allow the transitional zone to Treatment of visual defects remain in the screen’s periphery. As is the case in many disorders, a definitive The patient, being very motivated, also diagnosis of the cause of vision loss is not nec- developed treatments that worked well. He

712 The Journal of Family Practice | DECEMBER 2013 | Vol 62, No 12 TRAUMATIC AMMONIA EXPOSURE

would stare at a blank white wall approxi- ing and relaxation techniques. Once he was mately 2 feet away, focusing on one location. familiar with the techniques, he practiced One of his family members would take a laser them in the presence of the shed that con- pointer and start very far away, then slowly tained ammonia products, which was a trig- move the light closer to the patient’s center of ger for his anxiety. At first he was only able to vision. JD would tell his family member when approach the shed while using the breathing he could see the light and they would move exercises to calm his anxiety. Over several on to a different portion of his visual field. weeks, he became more comfortable moving After 3 months, we retested JD’s vision, closer to the shed, and he eventually stepped which showed great improvement. JD felt he into the shed and began staying for longer had significant improvement in his vision. The periods of time. The course of therapy took ophthalmologist retested JD about 2 months several months, but by the end of the sessions later and he passed a visual test well enough to he was able to perform necessary tasks in the obtain a modified driving license so he could shed with only mild anxiety. return to his work as an agronomist. He also suffered from persistent trou- bling nightmares that significantly affected Treatment of PTSD his sleep and led to physical symptoms of Therapy for PTSD is complex and best ap- headache and vomiting. These, too, were proached with a long-term, multifaceted overcome with the CBT approach.25 We in- plan.20 Both pharmacotherapy and psycho- structed him to immediately write down therapy can be considered for initial treat- as much as he could recall of a ment; however, no placebo-controlled upon waking from it. During the following randomized trials comparing the 2 mo- day, he re-read the dream and attempted to dalities have been conducted. Combination re-experience it while using the relaxation therapy can also be employed. techniques to temper anxiety. Over several Drug therapy, particularly selective se- months of therapy, his nightmares lessened rotonin reuptake inhibitors (SSRIs), has been and eventually stopped. shown to be generally effective in ameliorat- On the last day of therapy, JD reported he ing positive symptoms associated with PTSD, had 3 job offers and 2 more interviews lined such as nightmares and flashbacks. But they up, and that he was excited about his opportu- are less effective at treating negative symp- nities. We congratulated him on his visual re- toms such as withdrawal and avoidance.21,22 covery and applauded him for his hard work. There is no clinical evidence to support the use of anxiolytics such as benzodiaz- Discussion epines in treating PTSD-specific symptoms. While it is possible that JD spontaneously One small study did find a significant reduc- recovered his vision loss, it’s more likely that tion in anxiety with alprazolam compared treatment can be credited, given that he did with placebo; however, the response was not improve in the 6 months prior to treat- modest, and specific PTSD symptoms were ment and that his condition resolved over the unchanged.2 Given the high prevalence of 3-month rehabilitation period. comorbid in PTSD, benzo- Research that guides practice must nec- diazepines are best avoided since evidence essarily limit variables, but real-life patients for their effectiveness is lacking.23 often have multiple variables complicating Both CBT and eye movement desensitiza- both diagnosis and treatment. Our patient is tion and reprocessing (EMDR) can be effective a graphic example. He was exposed to anhy- therapy for PTSD.24 Both modalities center on drous ammonia with its multiple physiologic desensitization through exposure to traumatic sequelae and it was a traumatic event lead- recollections and symptom triggers. ing to additional sequelae. Furthermore, his The CBT approach we used focused on inability to perform his job and fulfill social JD’s phobic reaction to ammonia that pre- obligations contributed to his impairment. vented his return to work. First, he listened JD’s referral to a neural-ophthalmologist to relaxation CDs to practice deep breath- did not provide a definitive diagnosis. He Continued on page 718

jfponline.com Vol 62, No 12 | DECEMBER 2013 | The Journal of Family Practice 713 Continued from page 713 then followed up on a referral to the local likely help him, even if we were uncertain of residency clinic, where the family physician/ the absolute cause, he became an eager par- psychologist team treats patients from a bio- ticipant in his treatment. He also embraced psychosocial perspective. Although physi- the idea that it wasn’t up to the doctors alone cians feel most comfortable when they arrive to improve his condition, but that he could at a specific diagnosis with a specific evi- be an active participant. In our view, his en- dence-based treatment that predicts a good thusiastic efforts contributed to the ultimate outcome, this case yielded no definitive di- treatment outcome. agnosis. Instead, the psychologist and family Often family physicians think they should physician relied on general research findings refer these “complicated” patients to other spe- showing that in the context of traumatic in- cialists. However, for patients with combined jury or illness followed by debilitating anxiety psychological and physiological pathologies, symptoms, desensitization and rehabilitation we believe there are no better experts than provide the best chance of improvement. This family physicians. Properly trained family phy- shift in treatment approach very likely was sicians could have treated this patient without responsible for the patient’s improvement. the aid of a psychologist. Other patients who This approach had the added benefit of can benefit from this type of integrated bio- helping the patient feel empowered. When JD psychosocial rehabilitation include those with arrived at the consultation with the psycholo- chronic fatigue syndrome, chronic low back Others who gist and family physician, he was frustrated pain, and debilitating .26-28 JFP can benefit that no explanation had been found for his from integrated problem. As a result, he feared that nothing Correspondence Michael V. Bloom, PhD, Center for Family Medicine, 1115 biopsychosocial could be done. When told that a rehabilita- East Twentieth Street, Sioux Falls, SD 57105; michael. rehabilitation tion and gradual exposure approach would [email protected] are those with chronic fatigue syndrome, chronic low back References 1. Lessenger JE. Anhydrous ammonia injuries. J Agromedicine. pansion after visual restoration therapy. Clin Rehabil. 2010;24: pain, and 1996;3:191-203. 1027-1035. debilitating 2. Souther L, Small-Johnson J, Messing R. A description of agri- 17. Mueller I, Mast H, Sabel BA. Recovery of visual field defects: a cultural releases of anhydrous ammonia in Minnesota. Chem large clinical observational study using vision restoration thera- epilepsy. Health Safety. 2000;7:16-22. py. Restor Neurol Neurosci. 2007;25:563-572. 3. Welch A. Exposing the dangers of anhydrous ammonia. Nurse 18. Romano JG, Schulz P, Kenkel S, et al. Visual field changes after a Pract. 2006;31:40-45. rehabilitation intervention: vision restoration therapy. J Neurol 4. Makarovsky I, Markel G, Dushnitsky T, et al. Ammonia—when Sci. 2008;273:70-74. something smells wrong. Isr Med Assoc J. 2008;10:537-543. 19. Allen LA, Woolfolk RL. Cognitive behavioral therapy for somato- 5. Leveque T. Approach to the adult with acute persistent visual loss. form disorders. Psychiatr Clin North Am. 2010;33:579-593. In: UpToDate, Trobe J (ed), UpToDate, Waltham, MA, 2013. 20. Cukor J, Olden M, Lee F, et al. Evidence-based treatments for 6. Morgan A, Hemphill RR. Acute visual change. Emerg Med Clin PTSD, new directions, and special challenges. Ann N Y Acad Sci. North Am. 1998;16:825-843,vii. 2010;1208:82-89. 7. Beran DI, Murphy-Lavoie H. Acute, painless vision loss. J La State 21. Meltzer-Brody S, Connor K, Churchill E, et al. Symptom-spe- Med Soc. 2009;161:214-216, 218-223. cific effects of fluoxetine in PTSD. Intl Clin Psychopharmacol. 2000;15:227-231. 8. Vortmann M, Schneider JI. Acute monocular vision loss. Emerg Med Clin North Am. 2008;26:73-96. 22. Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder . Cochrane Database Syst Rev. 2006(1):CD002795. 9. Chamberlain MC, Chalmers L. Acute binocular blindness. Can- cer. 2007;109:1851-1854. 23. Braun P, Greenberg D, Dasberg H, et al. Core symptoms of post- traumatic stress disorder unimproved by alprazolam treatment. 10. American Psychiatric Association. Diagnostic and Statistical J Clin . 1990;51:236-238. Manual. 5th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2013. 24. Bisson J, Andrew M. Psychological treatment of post-trau- matic stress disorder. Cochrane Database Syst Rev. 2007(3): 11. Aybek S, Kanaan RA, David AS. The neuropsychiatry of conver- CD003388. sion disorder. Curr Opin Psychiatry. 2008;21:275-280. 25. Aurora RN, Zak RS, Auerbach SH, et al. Best practice guide for 12. Stone J, Vuilleumier P, Friedman JH. Conversion disorder: sepa- the treatment of nightmare disorder in adults. J Clin Sleep Med. rating “how” from “why.” Neurology. 2010;74:190-191. 2010;6:389-401. 13. Tocchio SL. Treatment of conversion disorder. A clinical and 26. Reid SF, Chalder T, Cleare A, et al. Chronic fatigue syndrome. Clin holistic approach. J Psychosoc Nurs Ment Health Serv. 2009; Evid (Online). 2008 Aug 28;2008:1101. 47:42-49. 27. Hall H, McIntosh G. Low back pain (chronic) Clin Evid (Online). 14. Mueller I, Gall C, Kasten E, et al. Long-term learning of vi- 2008 Oct 1;2008:1116. sual functions in patients after brain damage. Behav Brain Res. 2008;191:32-42. 28. Prevedini A, Presti G, Ragitti E, et al. Acceptance and commitment Therapy (ACT): the foundation of the therapeutic model and 15. Glisson CC. Capturing the benefit of vision restoration therapy. an overview of its contribution to the treatment of patients with Curr Opin Ophthalmol. 2006;17:504-508. chronic physical diseases. G Ital Med Lav Ergon. 2011;33(1suppl 16. Marshall RS, Chmayssani M, O’Brien KA, et al. Visual field ex- A):A53-63.

718 The Journal of Family Practice | DECEMBER 2013 | Vol 62, No 12